This proposal seeks continued funding of the Neuropathology and Tissue Culture Core to assist the overall program project grant in evaluating the pathogenesis of HIV-1-associated dementia and Progressive Multifocal Leukoencephalopathy (PML) and the cooperative molecular mechanisms through which HIV-1 and JC virus interact. We will provide neuropathological expertise fore the evaluation of surgical and autopsy brain tissue samples from AIDS and non-AIDS PML patients with HIV-1 encephalopathy and control tissue to complement molecular studies performed in Projects 1,2, and 3. We will provide highly purified cultures of microglia, oligodendrocytes, and astrocytes from human fetal CNS tissue as needed for the individual projects. The cultures will undergo quality control testing to ensure uniform distribution across the projects. We will provide cultures of established permanent cell lines, including the progenitor CG-4 cells and mouse embryo fibroblasts from Pur-alpha knockout mice as a service to all three projects. We will also offer on demand culturing of primary cells or establishment of cell lines from rats and genetically modified mice. The proposed Core services will provide essential and uniform material to the three participant projects to assist in their studies on the molecular biology of HIV-1 and JCV interaction with host cellular factors and will contribute to our understanding of the pathogenesis of these two CNS disorders.